ABSTRACT ? LABORATORY AND ANALYTICAL CORE The proposed projects of this application are concerned with reducing tobacco addiction through better understanding of how flavors and sweeteners influence behavior and addiction related to nicotine and tobacco. Research strategies include administration, by various routes, of nicotine alone, and nicotine in conjunction with other constituents, including menthol, flavors and sweeteners, followed by assessments of responses to nicotine. Optimal interpretation of study outcomes requires that variations in exposures to nicotine and/or flavor and sweetener constituents across individuals and experimental arms are considered. The primary objectives of the analytical laboratory core will therefore be to: 1) accurately identify and measure nicotine, flavors and sweeteners in tobacco products, and vapors produced from them; and 2) to provide objective estimates of exposures to such products by quantifying levels of nicotine, nicotine metabolites, and other constituents in biological fluids. The core will directly support all three projects and pilots of this proposal and will also be available to other tobacco research centers, including Rapid Response Projects announced by the FDA-CTP, on a cost reimbursement basis. Furthermore, the core will be able to set up other assays as mandated by the evolving needs of the center. To facilitate collaborations across other tobacco research centers, the core will generate a database of selected tobacco product constituents and biomarkers of exposure. Finally, all biological samples obtained in this Center will be maintained on site, in a frozen sample repository. The core will be led by Dr. Julie Zimmerman, who has considerable experience with chemical analysis of tobacco products, and Dr. Tore Eid, a clinical pathologist and neuroscientist who directed the core laboratory of the current NIH-funded Yale Tobacco Center of Regulatory Science (TCORS), and is an expert in chemical analysis of biological samples.